The invention relates generally to the dispensing of adhesive tissue sealants and other liquid preparations, including those requiring mixing immediately prior to use.
A variety of techniques have been used to bond or seal living tissue. For example, different types of tissues have been mechanically bound or sealed with a number of procedures, materials and methods including sutures, staples, tapes and bandages. In some applications, these materials are made of absorbable materials that are intended to bond and/or seal tissue as it heals and then to be absorbed over a period of time.
A recent addition to the techniques that can be used is application of an absorbable adhesive sealant composition to bond and/or seal tissue. The adhesive composition is readily formed from a two component mixture that includes a first part of a cross-linking agent and a second part of a protein, preferably a serum protein such as albumin. When the two parts of the mixture are combined, the mixture is initially liquid. The combined mixture then cures in vivo on the surface of tissue to give a substantive composition that securely bonds to the tissue. Additional details can be found in commonly owned U.S. Pat. No. 5,583,114, xe2x80x9cADHESIVE SEALANT COMPOSITION,xe2x80x9d to Barrows et al, the entire contents of which are hereby incorporated by reference.
Among the limitations on the widespread use of this material are that the first part, when rehydrated, has a limited shelf life and must be dissolved relatively shortly before use. Another limitation is that the two parts must be kept strictly separate until dispensed onto the tissue because the reaction time of the forming of the finished sealant is quite fast. These limitations increase the complexity for appropriate dispensing by the medical practitioner to form an effective adhesive tissue sealant on the tissue surface.
A known approach for dispensing two-part tissue sealants is to supply the user with a kit consisting of at least two syringes, vials containing the components in dry powder form, a syringe body for receiving and supporting both syringes, and a housing for connecting the two syringes to a common nozzle. The user fills the syringes by piercing the septums on the vials and withdrawing solution into the barrel of the syringe. If a component is in powder form within a vial, the user first injects a solvent and then withdraws the reconstituted solution. The needles on the syringes are removed, the syringe barrels and plungers are supported in housing, and the syringe nozzles are received in the housing.
Another approach is disclosed in U.S. Pat. No. 4,735,616 to Eibl. Dry powder is stored within both barrels of a dual barrel syringe. In each instance, the powder is stored on one side of a sliding plug, and solvent is stored on the other side. When the user presses down on the syringe plunger, the plugs slide along the barrels to positions at which the barrels each have a bulge that provides a bypass for the solvent to reach the powder.
In these prior art dispensers, the manifold passages connecting the two syringes to the common nozzle are typically narrow conduits of circular cross section. E.g., U.S. Pat. No. 4,631,055 to Redl.
Carpules have been used in some syringes; e.g., U.S. Pat. No. 3,767,085 to Cannon shows a dual carpule syringe for mixing compositions used in dentistry.
A kit for reconstitution and application of Tisseel(copyright) fibrin sealant including VH Sealer Protein and Thrombin solutions is currently available from Baxter Healthcare Corporation""s division of Glendale, Calif. The use of this product requires a complicated procedure. As a result, it is difficult to prepare the fibrin sealant with this kit and it is also difficult to use the applicator. Additionally, the applicator is said to suffer from clogging problems.
The Tisseel(copyright) kit comprises a first bottle containing freeze-dried thrombin, a second bottle with calcium chloride solution designed to reconstitute the thrombin; a third bottle with sealer protein concentrate, and a fourth bottle with fibrinolysis inhibitor solution. A Fibrinotherm(copyright) Heating and Stirring Device is used to heat and stir the components such as the sealer protein concentrate and the fibrinolysis inhibitor solution. Alternatively, a hot water bath or incubator may be used. This requires components to be heated above room temperature prior to use, further complicating the procedure.
The packaging of this device also causes problems. Two syringes and at least two (and preferably four) exposed needles are required simply to reconstitute the thrombin and sealer protein concentrate. For transfer of the Tisseel(copyright) VH solution and the Thrombin Solution to the sterile field in the operating room, the scrub nurse should withdraw the solutions while the circulating nurse holds the unsterile vials. This requires the coordination of two healthcare workers, one of which directs a sharp instrument (needle) toward the other. This is required twice to prepare the applicator of the product.
The packaging also includes multiple pouches that contribute to the waste and clutter at the location of medical care.
Outside the United States, a kit is available for use in preparing and dispensing the Beriplast(copyright) fibrin adhesive. This kit includes four vials with fibrinogen concentrate in a first vial, aprotinin solution in a second vial, thrombin in a third vial and calcium chloride solution in a fourth vial. An adapter with dual piercers is available in some kits which helps place the contents of one vial into another. However, once the two components of the fibrin adhesive are in solution form, the kit nevertheless requires two exposed needles to transfer the solutions from the mixed vials into the separate syringes of the delivery device. Since the external portion of the vials are considered non-sterile (i.e. all four vials are packaged in a box), it is believed that this kit also requires the coordination of two healthcare workers (one associated with the sterile field, one outside), one of which directs a sharp instrument (needle) toward the other.
The present invention provides an improved dispenser suitable for quickly and easily setting up and dispensing multi-part tissue sealants or other multi-part compositions requiring separation of the components until just prior to application on the tissue surface.
In a first aspect, the invention features a dispenser having a container (e.g., a carpule) with at least a portion of a first component of a multi-part tissue sealant and/or adhesive (e.g. a dry powder) having a septum at one end, an open end opposite the septum, and a movable plug. The powder may be retained at the septum end of the container by the movable plug, which is preferably displaced and pushed back as a solvent used for reconstituting the powder is introduced (e.g., through the septum). At least a portion (and preferably all) of a second component of the tissue sealant (e.g. a liquid) is contained within a second container, also with a movable plug. After the first component is reconstituted, a housing (preferably a manifold) having piercers is used to pierce both septums and allow the contents to be dispensed. Preferably, the piercers are placed in a protected position so as not to expose a user to contact with the piercers. A body supports the containers. Pistons are provided to advance the movable plugs.
Preferred implementations of the first aspect may include one or more of the following features.
The first component may be a dry powder of a water-compatible or water-soluble cross-linking agent.
The aqueous solution for dissolving the powder may be introduced through the first septum (e.g., either via the piercer or via an injection through the septum by a syringe).
The movable plug may be positioned in a position in which the space between the plug and the septum is substantially the minimum necessary to contain the dry powder, thereby reducing the amount of air in that space and consequently the amount of pressure rise associated with injecting liquid through the septum. The movable plug can move away from the septum as liquid is injected to reduce any pressure rise.
The second component stored in the second carpule may be a solution.
The second component may be a protein dissolved in an aqueous buffer and capable of reacting with the solution of the first component to provide the adhesive tissue sealant.
The body may comprise a retainer for protecting and/or holding the containers.
In a second aspect, the invention features an improved manifold for a two-part dispenser. Two containers (e.g., carpules), each having a septum at one end, an open end opposite the septum, and a movable plug, are supported in a dual syringe body, which has pistons configured to enter the open ends of the containers to advance the movable plugs. A manifold has cavities that receive the septum ends of the containers, and a disk supporting a piercer (e.g., hollow needle) is mounted in the base of each cavity so that the septum of a container is pierced when it is installed in a cavity. Each disk is supported a distance above the base of a cavity to form a plenum defined by the disk and adjacent walls of the base of the cavity. Liquid exiting a container travels through the lumen of the piercer, then into the adjacent plenum, and then out of the plenum along a conduit extending to the nozzle. This arrangement of disks each supporting a piercer and forming a plenum provides an effective, relatively low-cost way of constructing a manifold for connecting carpule piercers to a common nozzle.
Preferred implementations of the second aspect may include one or more of the following features.
Each disk may be sealed to the surrounding wall of the cavity (e.g., by an elastomeric sealing member on the disk) so that the adjacent plenum is defined by the disk and the base of the cavity.
The conduit and piercer lumen may each communicate with the plenum at laterally spaced apart locations so that flow from the piercer lumen to the conduit changes direction from a generally longitudinal flow path through the piercer lumen, to a generally lateral direction in the plenum, and then to a generally longitudinal flow path in the conduit.
The disk may be supported from the base of the cavity by standoffs.
The first container may contain a quantity of the first component in the form of a dry powder so that the first component must be dissolved prior to use by introduction of an aqueous solvent.
The second container may contain a quantity of protein in an aqueous buffer that is capable of reacting with a dissolved first component to provide an adhesive tissue sealant.
In a third aspect, the invention features a method for dispensing a component stored in a dispenser in dry powder form and reconstituted by introduction of a solvent. A carpule is provided with a septum at one end, an open end opposite the septum end, and a movable plug disposed therebetween. The dry powder is stored between the septum and the movable plug. Solvent is introduced into the interior of the container by piercing the septum with a syringe and injecting the solvent into the carpule. The carpule is installed in a syringe body and manifold, the latter providing a flow path from the piercer to an outlet nozzle.
Preferred implementations of the third aspect may include one or more of the following features.
Installing the carpule in the syringe body and manifold may occur before or after the solvent is injected through the septum.
The first movable plug may be positioned in a position in which the space between the plug and the septum is substantially the minimum necessary to contain the dry powder, thereby reducing the amount of air in that space and reducing the pressure increase within the carpule when the solvent is introduced by piercing the first septum. The movable plug can move away from the septum as liquid is injected to reduce any pressure rise.
The dispenser may comprise a second carpule comprising a second septum at one end, an open end opposite the second septum, and a second movable plug disposed therein, the second carpule containing a second component, and the syringe body and manifold may be sized and configured to accept the first and second carpule.
The second component may be a protein in an aqueous buffer and capable of reacting with the first component to provide an adhesive tissue sealant.
The dry powder of the first component may be a water-compatible or water-soluble cross-linking agent capable of reacting with the second component to provide the adhesive: tissue sealant.
In another aspect, the present invention comprises a kit having components useful for preparing and delivering a tissue sealant and/or adhesive having first and second components. The kit comprises a first container having a septum, at least a portion of the first component stored therein, and outer portions. The kit includes a second container having at least a portion of the second component therein, a septum, and outer portions. At least one vial with a solvent for at least one of the first and second components is also present in the kit. The kit further includes a syringe and needle; and a sterile housing having first and second piercers located in protected positions and a portion that is sized and shaped to receive the first and second containers.
In another aspect, the present invention comprises a method of preparing a multiple component tissue sealant and/or adhesive just prior to use comprising the steps of providing a first container having a septum and a dry powder stored therein; providing a second container having a septum and a liquid therein; providing a vial with a solvent for the dry powder therein; providing a syringe and needle; providing a housing having first and second piercers located in protected positions and a portion that is sized and shaped to receive the first and second containers; withdrawing the solvent from the vial with the syringe and needle; placing the solvent in the first container; and installing the first and second containers in the housing and piercing the septums of the first and second containers with the first and second piercers without exposing a user to physical contant with the piercers.
The invention provides a significantly simpler and easier to use dispenser, one particularly well suited to handling adhesive tissue sealants. It is also simple and relatively inexpensive to manufacture. It delivers excellent performance, and is particularly good at mixing solutions reconstituted from dry powder.